A rigorous in silico genomic interrogation at 1p13.3 reveals 16 autosomal dominant candidate genes in syndromic neurodevelopmental disorders.

Genome-wide chromosomal microarray is extensively used to detect copy number variations (CNVs), which can diagnose microdeletion and microduplication syndromes. These small unbalanced chromosomal structural rearrangements ranging from 1 kb to 10 Mb comprise up to 15% of human mutations leading to monogenic or contiguous genomic disorders. Albeit rare, CNVs at 1p13.3 cause a variety of neurodevelopmental disorders (NDDs) including development delay (DD), intellectual disability (ID), autism, epilepsy, and craniofacial anomalies (CFA). Most of the 1p13.3 CNV cases reported in the pre-microarray era encompassed a large number of genes and lacked the demarcating genomic coordinates, hampering the discovery of positional candidate genes within the boundaries. In this study, we present four subjects with 1p13.3 microdeletions displaying DD, ID, autism, epilepsy, and CFA. In silico comparative genomic mapping with three previously reported subjects with CNVs and 22 unreported DECIPHER CNV cases has resulted in the identification of four different sub-genomic loci harboring five positional candidate genes for DD, ID, and CFA at 1p13.3. Most of these genes have pathogenic variants reported, and their interacting genes are involved in NDDs. RT-qPCR in various human tissues revealed a high expression pattern in the brain and fetal brain, supporting their functional roles in NDDs. Interrogation of variant databases and interacting protein partners led to the identification of another set of 11 potential candidate genes, which might have been dysregulated by the position effect of these CNVs at 1p13.3. Our studies define 1p13.3 as a genomic region harboring 16 NDD candidate genes and underscore the critical roles of small CNVs in in silico comparative genomic mapping for disease gene discovery. Our candidate genes will help accelerate the isolation of pathogenic heterozygous variants from exome/genome sequencing (ES/GS) databases.

Oral Health-Related Quality of Life in Anticoagulated Patients with Warfarin Treatment: A Cross-Sectional Study.

To evaluate factors associated with oral health-related quality of life (OHRQoL) in patients under oral anticoagulant therapy with warfarin, a cross-sectional study was conducted. Validated questionnaires assessed self-reported periodontal disease, demographic variables, and OHRQoL using the short version of the Oral Health Impact Profile (OHIP-14) instrument. After calibration (Kappa > 0.60), an examiner evaluated patients' experience with dental caries and the need for dental prostheses. Statistical analysis involved proportions and measures of central tendency. Negative binomial regression models were used to estimate the rate ratios (RR) and the corresponding 95% confidence interval (CI). The sample consisted of 158 individuals, with a mean age of 58.8 years (SD = 12.1), of which 62.7% of the participants were women. The OHIP-14 mean was 10.62 (SD = 10.92). A higher OHIP-14 total score (worse OHRQoL) was associated with ethnic group, age, periodontal disease self-report, dental caries, and oral health self-report. Demographic and clinical factors can negatively influence the perception of anticoagulated patients on OHRQoL.

Dental Caries Remains a Significant Public Health Problem for South American Indigenous People.

ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Dental caries in South American Indigenous people: A systematic review. Soares GH, Pereira NF, Gabriela M, Biazevic H, Braga MM, Michel-Crosato E. Community Dent Oral Epidemiol 2019;47(2):142-52. SOURCE OF FUNDING: Brazilian National Council for Scientific and Technological Development (CNPq). TYPE OF STUDY/DESIGN: Systematic review with meta-analysis.